title: Evidence for phenylalanine zipper-mediated dimerization in the X-ray crystal structure of a magainin 2 analogue.
abstract: High-resolution structure elucidation has been challenging for the large group of host-defense peptides that form helices on or within membranes but do not manifest a strong folding propensity in aqueous solution. Here we report the crystal structure of an analogue of the widely studied host-defense peptide magainin 2. Magainin 2 (S8A, G13A, G18A) is a designed variant that displays enhanced antibacterial activity relative to the natural peptide. The crystal structure of magainin 2 (S8A, G13A, G18A), obtained for the racemic form, features a dimerization mode that has previously been proposed to play a role in the antibacterial activity of magainin 2 and related peptides.
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Hayouka
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Mortenson
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Dale F
authors.initials: DF
authors.lastname: Kreitler
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Weisblum
authors.affiliation: Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Katrina T
authors.initials: KT
authors.lastname: Forest
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D018360:Crystallography, X-Ray; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D016984:Enterococcus faecium / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D054806:Magainins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010649:Phenylalanine / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D029867:Xenopus Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D054806:Magainins; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D010649:Phenylalanine